Abstract 3058: AR-dependent anticancer action of BF175 in hormone sensitive prostate cancer

Abstract Androgen receptor (AR) is a well established key biological contributor to prostate cancer progression. Despite significant efforts which have resulted in the therapeutic agents that target the AR signaling being the therapy of choice, prostate cancer remains one of the topmost causes of cancer-related deaths among men in the United States. Hence, development of novel targeted therapeutics that augment or supplant AR-based therapy remains a top priority. Sterol regulatory element binding proteins (SREBPs)are a family of transcription factors, consisting of SREBP-1 and SREBP-2, that control lipid synthesis. Available literature provides evidence for the cooperation between SREBPs and AR signaling in promoting prostate cancer progression. We observed that the SREBP expression is higher in LNCaP, C4, and C4-2 AR-positive/androgen-dependent compared to DU145, and PC3 AR-negative/androgen-independent prostate cancer cell lines. Therefore, we hypothesized that pharmacological targeting of SREBPs might be a promising therapeutic approach in hormone sensitive prostate cancer. We developed a novel boron-containing small molecule inhibitor of SREBPs, BF175, whose anticancer activity against prostate cancer has not been elucidated. In our study, we investigated the AR-dependent anticancer activity of BF175 in prostate cancer. We observed inhibition of viability, proliferation, and metastatic potential as well as induction of apoptosis in all prostate cancer cell lines treated with BF175. We also observed reduction in the levels of SREBPs in all prostate cancer cell lines treated with BF175. Notably, the anticancer action of BF175 was dependent on the AR status and BF175 demonstrated significantly more potent anticancer action in AR-positive/androgen-dependent compared to AR-negative/androgen-independent prostate cancer cell lines. Altogether, our data shows that BF175 may be a potential novel therapeutic agent for hormone sensitive prostate cancer. Citation Format: Lakshmi Sirisha Devarakonda, Prashanth Parupathi, Ekniel Francois, Bhasker C. Das, Avinash Kumar. AR-dependent anticancer action of BF175 in hormone sensitive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3058.